Recent developments and obstacles in the treatment of melanoma with BRAF and MEK inhibitors

Document Type

Article

Publication Date

5-1-2018

Publication Title

Critical reviews in oncology/hematology

Abstract

Metastatic melanoma is a least common form of cancer as it accounts only for 1% of all cancer cases. But, it is most deadly in nature and is haunting mankind for long emotionally as well as economically. The sites for the onset of the disease are pigment-producing cells of the skin, mucosa, eye etc. It has the potential to spread other sites like subcutaneous tissue, lymph nodes, lungs, liver, bone and brain. The United States Food & Drug Administration has approved various drug molecules from time to time. The molecules (Dabrafenib-BRAF inhibitor and Trametinib-MEK inhibitor) have proved their credentials alone and in combination as well. These molecules have demonstrated good results for various end points like median progression free survival, overall survival, objective response etc. The median progression free survival for patients using dabrafenib and trametinib were 5.1 and 4.8 months, respectively (administered singly). It has increased to 11.4 months in the combination treatment "dabrafenib + trametinib", which is approximately 104% and 138% greater than dabrafenib and trametinib treated groups alone. Similarly, the overall survival rate and objective response rate for the patients administered with "dabrafenib + trametinib" have been increased by 72% 64%, respectively. All these increments in these parameters were for a short period of time as the molecules were unable to withstand the pressure of resistance developed in the patients. So, the current review suggests the use of BRAF and MEK inhibitors as intermittent therapy along with heat shock protein 90 (HSP90) molecules.

Medical Subject Headings

Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Melanoma; Mitogen-Activated Protein Kinase Kinases; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Survival Rate; Therapies, Investigational

PubMed ID

29650281

Volume

125

First Page

84

Last Page

88

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